This competing renewal application requests funding for Years 8-12 to continue study of the onset, course, causes, and consequences of drug use and drug use disorders in The Pittsburgh ADHD Longitudinal Study (PALS). 364 children with ADHD (probands) were ascertained in their elementary school-aged years following their participation in the ADHD Program at WPIC, University of Pittsburgh. This is the largest study of its kind: rigorously diagnosed ADHD in childhood, detailed comprehensive childhood data (including standardized and objective data on both symptoms and impaired functioning in multiple domains), and detailed annual follow-up assessments of drug abuse and dependence and related domains (e.g., academic/vocational functioning, social relations, parent characteristics). NonADHD, demographically similar controls (n=240) were recruited at follow-up initiation, when participants were 11 to 25. Using a cohort-sequential design, all participants have been followed annually since recruitment;retention is over 90% and a multiple reporter approach has been adopted throughout. A sampling of findings includes: 1) earlier start of use and a higher risk for heavy marijuana and cigarette use in proband adolescents;2) absence of proband-control differences for marijuana use and disorder at 18-25 yrs when controls are also using marijuana heavily (unless concurrent ASP is considered);3) positive association between duration of lifetime stimulant treatment and early adulthood marijuana and cigarette use, 4) weak associations between childhood conduct problems and later drinking outcomes but strong concurrent associations, supporting an ADHDFconductFSUD pathway, and 5) considerable evidence of family adversity and poor school functioning in the probands. Continued follow-up (annual to age 25, age-targeted periodic assessments thereafter) is requested to determine whether early drug use patterns persist through the twenties when desistance is the U.S. norm, to determine whether new cases of SUD, particularly of non-marijuana illicit drugs, which have low rates in our participants to date, develop in the mid-to-late 20s, and to study the putative causal mechanisms underlying these SUD developments and consequences in early adulthood. PUBLIC HEALTH RELEVANCE: This is a large long-term study of drug use and dependence in people who were diagnosed with Attention- Deficit/Hyperactivity Disorder (ADHD) in childhood and will help explain why children with ADHD are at risk of drug use and dependence, including what factors contribute to the risk and what factors decrease the risk. ADHD is one of the most frequently diagnosed mental health problems of children in the United States;drug use and dependence risk in these individuals carries large direct and indirect costs to society. This study will provide information to improve prevention as well as treatments for drug use problems in this large group of high risk children in the U.S.